tbuckley/cabot-search huggingface dataset:
NFB-15. "Cognitive Impairments in Children and Adolescents with Neurofibromatosis"
Authors: Kalliopi Mavrea, Eleftheria Kokkinou, Kleoniki Roka, Stavroula Tsiorou, Danae Deligeorges, Christina Kanaka-Gantenbein, Flora Bacopoulou, Roser Pons, Antonis Kattamis
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION-BACKGROUND: Cognitive, learning and/or behavioral disorders are common (up to 70%) complications of neurofibromatosis (NF). The first multidisciplinary-clinic for neurocutaneous-disorders was established at the Aghia Sophia Children’s Hospital in Athens, Greece, in 2016. Since then, more than 200 children and adolescents with NF have been examined. SCOPE: Acknowledging and indicating awareness on the devastating life-long consequences (poor academic performance, behavioral problems, and limited career prospectives) that can result from cognitive impairment, a research collaboration with educational specialists was recently implemented to examine the neurocognitive functions of children and adolescents with NF. MATERIALS: Children and adolescents aged 7-14 years who suffer from NF type I or type II, were eligible for study entry. The third edition of the Wechsler Intelligence Scale (WISC-III) was used to measure participants’ cognitive function. RESULTS: Preliminary results of this ongoing study are presented. Patients’ recruitment was limited by the coronavirus disease 2019 (COVID-19) restrictions. At this stage, the research involved 10 participants suffering from NF, with mean (± SD) age of 11.55 (± 1.80) years and a male-to-female ratio of 1. The mean (± SD) full-scale intelligence quotient (IQ) was 85.50 (± 18.80), corresponding to the 0.3rd to 73th percentile range. The mean (± SD) scores of performance IQ and verbal IQ were 84.90 (± 17.43) and 89.40 (± 17.23) respectively, corresponding to the 1st to 73rd percentile range for both subscales. CONCLUSION: Significant cognitive deficits, according to the percentile scores of WISC-III, were demonstrated in the small number of children and adolescents suffering from NF (type I or type II). Cognitive assessment, as part of the multidisciplinary approach of these patients is warranted, to aid timely educational interventions and improve patient learning outcomes.
ATRT-15. Primordial germ cells identified as one potential cell of origin of MYC rhabdoid tumors
Authors: Monika Graf, Marta Interlandi, Natalia Moreno, Rajanya Roy, Dörthe Holdhof, Carolin Göbel, Viktoria Melcher, Julius Mertins, Thomas K Albert, Dennis Kastrati, Amelie Alfert, Till Holsten, Flavia de Faria, Michael Meisterernst, Claudia Rossig, Monika Warmuth-Metz, Johannes Nowak, Gerd Meyer zu Hörste, Chloe Mayère, Serge Nef, Pascal Johann, Michael C Frühwald, Martin Dugas, Ulrich Schüller, Kornelius Kerl
Journal: Neuro-Oncology (2022)

Abstract Rhabdoid tumors (RT) are embryonal neoplasms occurring most frequently in the central nervous system where they are termed atypical teratoid rhabdoid tumor (ATRT). A common hallmark of RT is homozygous loss of the BAF complex subunit SMARCB1. RT patients have a poor prognosis with an overall survival time of 17 months and &amp;gt;60% of patients suffer from relapses. The lack of an optimal treatment strategy could be attributed to the heterogeneity within and between different subgroups of ATRT. Despite the recent advancements in characterizing RT at a molecular level, the cellular origin of RT remains elusive. Thus, this study focused on the identification of the cellular origin of MYC-RT and underlying epigenetic deregulations which account for the cellular heterogeneity in these tumors. We showed that Smarcb1 abrogation in Sox2-positive progenitor cells at E6.5 give rise to RT of the MYC and SHH subgroup in genetically engineered mouse models (GEMM). To uncover distinct cells of origin (COO) for the SHH and MYC subgroups, unbiased computational approaches were used to compare single-cell transcriptomes of GEMMs with single-cell reference maps of murine early embryogenesis. While SHH tumors arise from mid/hindbrain progenitor cells, primordial germ cells (PGCs) emerge as COO of both intracranial and extracranial MYC tumors. PGCs as COO of MYC-RT were validated in vivo by using PGC-specific Smarcb1 knockout mouse model. We further characterized a deregulated transcriptome in MYC-RT compared to PGCs, which is sustained by a subset of epigenetically driven tumor cells. Deregulated expression of genes driving methylation/demethylation processes in MYC tumors and regression of these tumors upon treatment with decitabine in vitro and in vivo, indicates that DNA methylation plays a key role in cellular transformation and development of MYC-RT.
Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment
Authors: Lihong Wang, Louisa S Chard Dunmall, Zhenguo Cheng, Yaohe Wang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Tumor cells manipulate the local environment in which they grow, creating a tumor microenvironment (TME) that promotes tumor survival and metastasis. The TME is an extremely complex environment rich in immunosuppressive cells and cytokines. Various methods to therapeutically target the complicated TME are emerging as a potential approach for cancer treatment. Oncolytic viruses (OVs) are one of the most promising methods for remodeling the TME into an antitumor environment and can be used alone or in combination with other immunotherapy options. OVs replicate specifically in tumor cells and can be genetically engineered to target multiple elements of the TME simultaneously, thus representing a therapeutic with the potential to modify the TME to promote activation of antitumor immune cells and overcome tumor therapeutic resistance and recurrence. In this review, we analyze the tropism of OVs towards tumor cells and explore the interaction between OVs and immune cells, tumor stroma, vasculature and the metabolic environment in detail to help understand how OVs may be one of our most promising prospects for long-term curative therapies. We also discuss some of the challenges associated with TME therapies, and future perspectives in this evolving field.
An evaluation of screening pathways using a combination of MRI and PSA: Results from the IP1-PROSTAGRAM study
Authors: M.J. Connor, D. Eldred-Evans, H. Tam, H. Sokhi, A.R. Padhani, D. Price, M. Gammon, N. Klimowska-Nassar, P. Burak, E. Day, M. Winkler, F. Fiorentino, H.U. Ahmed
Journal: European Urology (2022)
Integrated analysis of transcriptome profiles in lung adenocarcinoma with spread through air spaces.
Authors: Bo Pan, Dexin Jia, Jianxiong Geng, Chengwei Cui, Yan Yu
Journal: Journal of Clinical Oncology (2022)

e21103 Background: Spread through air spaces (STAS) is a recently described invasive pattern of lung cancer with a relatively poor prognosis. The current study aims to evaluate and compare the transcriptome patterns and tumor microenvironment (TME) of STAS positive and negative lung adenocarcinoma (LUAD) cases. Methods: Nineteen LUAD patients who underwent radical surgery were enrolled in the current study, of which 11 were STAS-positive and 8 were STAS-negative. We performed RNA sequencing and data analyzes of the patient’s resected primary tumor tissue samples in a College of American Pathologists accredited laboratory (Genecast Biotechnology Co., Ltd, Wuxi). Results: A total of 841 differently expressed genes (DEGs) were identified between STAS positive and negative groups, including 442 up-regulated and 399 down-regulated DEGs in STAS positive tumors. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the 841 DEGs were significantly enriched in humoral immune response, cell adhesion molecules, and IL-17 signaling pathways, and so on. Moreover, hypoxia VHL targets up was exceedingly up-regulated in STAS positive tumors through gene set enrichment analysis (GSEA). In addition, the abundance of regulatory T cells (Tregs) showed a borderline significant trend to be higher in STAS positive cases. Conclusions: Our study is the first to report the transcriptome profiles and TME of LUAD patients with STAS. These novel findings may add to further understanding underlying biological mechanisms of STAS occurrence and help developing rationale treatments to deliver more survival benefits for STAS positive LUAD patients.
Preliminary results from phase Ib/II neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).
Authors: Roger Li, Philippe E. Spiess, Wade J. Sexton, Scott Michael Gilbert, Michael Adam Poch, Julio M. Pow-Sang, Jingsong Zhang, Jasreman Dhillon, Kerry Thomas, Gustavo Borjas, Juliet Bala, Paola Grandi, James Burke, James J Mule, Jose Conejo-Garcia, Rohit K. Jain
Journal: Journal of Clinical Oncology (2022)

4574 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x10 12 vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results from a prespecified interim analysis following accrual of 15 patients is reported herein. Results: Between Nov 2020 and Jan 2022, 15 pts were enrolled with median age 75.5yrs, 73% male, 47% &gt; cT2; 1 patient refused RC but was included in the ITT population. No DLTs were encountered. The overall rate of grade 3-4 AEs was 10/15 (75%), and the vast majority were related to RC (90%). Immune related AEs were seen in one pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. PaR was observed in 6/13 (46%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 54%. Clinical trial information: NCT04610671. [Table: see text]
Effect of neoadjuvant versus adjuvant chemotherapy on ipsilateral breast tumor recurrence after breast-conserving surgery and whole-breast irradiation.
Authors: Jong-Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han
Journal: Journal of Clinical Oncology (2022)

604 Background: Early Breast Cancer Trialists’ Collaborative Group conducted a large meta-analysis and reported that patients who underwent neoadjuvant chemotherapy (NAC) had higher ipsilateral breast tumor recurrence (IBTR) rate than those with adjuvant chemotherapy. However, since the study was conducted with patients treated two decades ago, the results could not reflect the advance in treatments and IBTR rate was much higher than in recent studies, Thus, we investigated the association between chemotherapy settings and IBTR rates in breast cancer patients. Methods: We retrospectively reviewed the data of 5,307 patients who underwent breast conserving surgery followed by whole breast irradiation between January 2004 and December 2018 in a single institution. Patients who underwent mastectomy or omitted chemotherapy were excluded. Results: The 1,473 patients who underwent NAC showed significantly higher IBTR rate than the 3,564 patients who underwent adjuvant chemotherapy (10-year risk: 4.5% vs. 4.0%; log-rank p=0.045, hazard ratio 1.42 [95%CI,1.01-1.99]). The difference was more evident for patients with hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER2) negative tumor (unadjusted p=0.001, hazard ratio 2.27 [95%CI,1.37-3.74; adjusted p=0.002, hazard ratio 2.80 [95%CI,1.45-5.42]], and the statistical significance was still remained after 1:1 propensity score matching (p=0.026). In contrast, patients with other subtypes did not show significant differences between two groups. Conclusions: Patients who underwent NAC for HR+/HER2- tumors carry increased risk of IBTR than those who underwent adjuvant chemotherapy. Our observation supports the need for considering tumor subtypes in initial treatment. In addition, more intensive surveillance would be needed for patients with HR+/HER2- tumors after NAC.
Real-time Estimation of Nephron Activity with a Linear Measurement System (RENAL-MS) obviates the need for nuclear medicine scans to predict estimated glomerular filtration rate after nephrectomy
Authors: J. Schober, M. Loecher, D. Strauss, E. Cho, A. Castro Bigalli, K. Ginsburg, A. Kutikov, M. Strother
Journal: European Urology (2022)
Multicenter prospective clinical trial of molecular genetic markers for non-invasive differential diagnosis of benign and malignant melanocytic skin lesions.
Authors: Igor Samoylenko, Andrew R Zaretsky, Lidia V Chudakova, Oleg V Drozd, Oksana E Garanina, Irena L Shlivko, Grigory Zinovev, Kirill A Baryshnikov, Kristina V. Orlova, Tatiana Maximova, Igor Sinelnikov, Anna Kim, Irina N. Mikhaylova, Lev V. Demidov
Journal: Journal of Clinical Oncology (2022)

e21581 Background: Improving the accuracy of non-invasive diagnosis of skin tumors is becoming an urgent problem, given the clear increase in the incidence of melanoma in many countries. Dermoscopy and examination by an experienced dermatologist can reduce the NNE to 5–10 per melanoma (M) detected, however, achieving even this, clearly suboptimal, rate requires a long specialist training. Methods: We report results of prospective nonrandomized trial evaluating sensitivity and specificity of RNA profiling of cytological samples from adhesive transparent patches (ATP) applied to skin lesions. Routine pathology reports were obtained for all surgery samples. RNA extracted from ATP specimens (N = 126) was tested for mRNA expression of PRAME and LINC00518 genes. GAPDH was used as a reference gene. Sample was considered marker-positive if either PRAME or LINC00518 expression was detected. Results: Between June 2021 and November 2021, 126 pts undegoing excisional biopsy of skin lesions were included in the study at 5 centers. On pathology, invasive M was detected in 49 (38.9%) patients (mean Breslow thickness was 2.41 mm [95%CI 1,44 to 3.37]), M in situ in 6 (4.8%), non-melanoma skin cancer in 4 (3.2%) and dysplastic nevus in 56 (44.4%). In the day of preplanned excision ATP was applied to the target lesion for 5–6 min and sent to the central lab. Amplifiable mRNA was found in all 126 ATP samples. 82 samples of 126 (65,1%) tested marker-positive. Sensitivity of RNA profiling for detection of skin cancers reached 88.14% (95% CI 77.07% – 95.09%), while specificity was only 53.85% (41.03% – 66.30%), with PPV of 63.41% (56.74% – 69.61%), NPV of 83.33% (70.65% – 91.22%) and accuracy of 70.16% (61.29% – 78.04%). Among the seven false negative results there were 3 M in situ and 4 invasive M. Conclusions: RNA profiling of skin ATP specimens is feasible and has high sensitivity but rather low specificity. Randomized studies are needed to evaluate if this technique can add anything to dermoscopy or other noninvasive diagnostic modalities. Clinical trial information: NCT04353050. [Table: see text]
Comparative assessment of clinical effectiveness of ICSI, PICSI and testi-ICSI procedures in overcoming in patients with high level of Sperm DNA Fragmentation (SDF)
Authors: M. Korshunov, E.S. Korshunova, D.M. Korshunov, M.N. Komarova, E.V. Ekimova, L.B. Kindarova, S.P. Darenkov
Journal: European Urology (2022)
Survival outcomes after omission of surgery for ductal carcinoma in situ: A National Cancer Database (NCDB) analysis.
Authors: Elizabeth C Poli, Wenli Dong, Simona Flora Shaitelman, Nina Tamirisa, Gildy Babiera, Yu Shen, Isabelle Bedrosian
Journal: Journal of Clinical Oncology (2022)

e12574 Background: Clinical trials of active surveillance (AS) for Ductal Carcinoma in Situ (DCIS) are underway. We sought to understand the historical management of biologically favorable DCIS and to determine the long-term outcomes of patients who did not have surgery at time of diagnosis. We hypothesized that women who had biologically favorable DCIS and underwent AS would have excellent long-term outcomes. Methods: The NCDB was queried from 2004 to 2017 for women diagnosed with DCIS. This cohort was further refined to identify those with biologically favorable DCIS defined as grade 1 or 2 and hormone receptor (HR) positive. Women under age 40 were excluded. AS was defined as either no surgery or surgery &gt;12 months from diagnosis. A Cochran-Armitage test was used to assess the trend of surgery omission over year of diagnosis. Multivariable logistic regression was used to assess association between baseline factors and AS. Kaplan-Meier curves were estimated to show overall survival (OS) in this biologically favorable DCIS group that underwent AS, stratified by age (&lt;50, 50-65, &gt;65). Univariate and multivariable Cox proportional hazard models were used to determine the effects of prognostic factors on survival distributions. Results: There were 74,868 women with grade 1 or 2, HR positive DCIS, of whom 2,384 (3.2%) were treated with AS. The proportion of patients with biologically favorable DCIS who underwent AS increased over time, peaking in 2017 with 4.2% of DCIS cases diagnosed that year treated with observation (p&lt;0.001). Only 17% of the patients in the AS group received hormonal therapy. On multivariable analysis, increasing age (OR 1.02, p&lt;0.001), black race (OR 1.7, p&lt;0.001), and being uninsured (OR 2.2, p&lt;0.001) were all associated with increased likelihood of AS. In an unadjusted analysis, receipt of surgery was associated with improved OS in the entire cohort. However, the OS benefit from surgery differed when stratified by age. In women &lt;50 years of age, OS outcomes were similar, with 10-year OS of 97.4% in the immediate surgery cohort vs 99.1% in AS cohort (p=0.43). In contrast, in women &gt;50 years of age, 10-year OS was higher for women undergoing surgery (85.3% vs 70.0% in AS group, p &lt;0.001). This association with OS in this older cohort persisted even after adjusting for age, race and comorbidity as well as facility demographics. Conclusions: The proportion of patients with low or intermediate grade, hormone receptor positive DCIS not treated with surgery has remained small but is increasing over time. AS of biologically favorable DCIS in younger, healthier women is not associated with adverse survival. In older women, the finding of benefit of surgery over AS is very likely confounded by underlying health factors that are not fully captured with co-morbidity scores.
MEDB-65. Molecular subclassification of a national cohort of pediatric medulloblastoma based on methylation profile
Authors: Lide Alaña, Idoia Martin-Guerrero, Aurora Navajas, Laura Zaldumbide, Lorena Mosteiro, Edward C Schwalbe, Debbie Hicks, Steven C Clifford, Miguel García-Ariza
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Pediatric Medulloblastoma (MB) accounts for approximately 20% of all childhood brain tumors. Molecular subgroups namely WNT, SHH, Group 3 and Group 4, exhibit divergent biology, and clinical outcomes. DNA methylation analysis is a robust option to classify pediatric MB into molecular subgroups, which allows the optimization of diagnosis and stratification of the treatment. We review the first experience of molecular subclassification carried out at the national level in our country. METHODS: Multi-center centralized prospective and retrospective study of frozen tumor samples at diagnosis from pediatric MB patients diagnosed in Spanish hospitals, from April 2021 to December 2021. A registry was created with histology review, immunohistochemical (IHC) subgrouping, and a molecular subgrouping based on the Minimal Methylation Classifier (MIMIC) from Schwalbe et al., 2017. The time from the sample centralized reception to the study result was also collected. RESULTS: 25 frozen MB tumor samples from patients at diagnosis were included. 6 were retrospective and 19 prospective. IHC classified 19 cases (76%) as non-WNT/non-SHH MBs, 3 (12%) as WNT-activated and 3 (12%) as SHH-activated. MIMIC classified, in the non-WNT/non-SHH, 6 tumors (24%) as Group 3 and 13 (52%) as Group 4. 2 cases (8%) were WNT-activated MBs and 3 (12%) were SHH-activated MBs. Only 1 case (4%) was unclassified by MIMIC (WNT using IHC). Comparing both methods (IHC and MIMIC), diagnosis agreed in 96% of cases. The response time ranged from 5 to 10 days. CONCLUSIONS: DNA methylation profiling has proven to be a robust and quick option to classify MB into subgroups and it correlates with the IHC diagnosis. This tool was successfully implemented in our national routine diagnosis, enabling a reliable and rapid molecular subgrouping classification.
A five-year epidemiological profile of patients with cancer managed by a Haitian cancer program.
Authors: Joseph Bernard, Rebecca Rose Henderson, Lenz Sacha Christyl Pierre, Lynn Gabrielle Alexis, Doukens Patrick Gilbert, Vincent DeGennaro
Journal: Journal of Clinical Oncology (2022)

10564 Background: Cancer epidemiology in Haiti is poorly understood. The national cancer registry is not functional, and data reported by GLOBOCAN are estimations that do not totally reflect the reality of cancers in Haiti. The aim of this study was to present the five-year epidemiology of malignancies managed by one of the main cancer programs in Haiti. Methods: A retrospective study was conducted on patients aged 15 years old and above with pathological and/or clinical diagnosis of cancer managed from January 2016 to December 2020 at Innovating Health International (IHI), a cancer center located in Port-au-Prince, Haiti. The chart review collected variables such as age, gender, date of admission and cancer type in order to present this epidemiological profile of cancers. Results: Overall, 3060 patients with cancer were managed during the study period. 84.4% of the patients were female and 15.6% male. The mean and median ages of the study population were respectively 52.5 [range: 15 –92] and 53.0 years. Adolescents and young adults (15-39 years old) represented 18.9 % of this cohort and geriatric cases (≥ 65 years old) were 21.0%. Breast cancer was the most common type (n = 1391, 45.5%%), followed by gynecological cancers (n = 746, 24.4%) with cervical cancer representing 77.5 % of these cases (n = 578); gastrointestinal cancers (n = 252, 8.2%) dominated by colorectal (n = 92, 36.5%) and gastric cancer (n = 58, 23.0%); head and neck cancers (n = 129, 4.2%); hematological malignancies (n = 128, 4.2%) with lymphomas representing 60.9% of the cases (n = 78); sarcomas (n = 114, 3.7%), urological cancers (n = 73, 2.4%) with prostate cancer representing 56.1% of the cases; skin cancers including melanoma (n = 60, 1.9%); lung cancer (n = 24, 0.8%); thyroid cancer (n = 13, 0.4%) and central nervous system (CNS) cancers (n = 6, 0.2%). 4.1% of the patients (n = 124) had a cancer of unknown primary (CUP). Breast (53.5%), cervical (28.9%) and gastrointestinal (5.0%) cancers were the most common types among women, while gastrointestinal (25.8%), hematological (16.1%), head and neck (14.7%) and urological (12.6%) cancers were the most diagnosed among men. Conclusions: Cancer mainly affects Haiti’s young, active and female population. Breast and cervical cancers were the most prevalent in this retrospective cohort regardless of the age group. The under-representation of prostate and other urological malignancies, lung cancer, acute leukemias and CNS cancers was likely due to underdiagnosis, misdiagnosis, under-referral or early mortality. An active cancer registry is needed to better evaluate the real cancer burden in Haiti.